Strike the parasite and spare the host.

Strike the parasite and spare the host

Recent research by two scientific teams offers new hope for curing Chagas disease and leishmaniasis, parasitic diseases that kill millions each year and for which no effective drugs exist. The scientists appear to have overcome the first stumbling block in treating any parasitic disease: killing the parasite without harming the human host.

One team accomplished this by developing drugs that interfere with an enzyme found in parasites causing Chagas disease and leishmaniasis but not in humans. Chagas disease ravages the heart; leishmaniasis ulcerates the skin and internal organs. Normally, the enzyme works with a compound called trypanothione to destroy oxygen free radicals, toxic by-products of cellular activity. Humans produce an analogous enzyme, but with a different structure. Graeme Henderson and Peter Ulrich at Rockefeller University in New York and their colleagues proposed that disrupting the reaction between the enzyme and trypanothione would block the parasites.

The scientists created a series of compounds designed to masquerade as trypanothione and lure the enzyme away from the true trypanothione. Surprisingly, says Ulrich, "the compounds went one step further." They worked with the enzyme to produce toxic free radicals, essentially turning the parasite's defensive enzyme into a suicide weapon, the researchers report in the August PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (Vol.85, No.15). When the group administered three of the drugs to cultured human smooth-muscle cells infected with Chagas disease parasites, one drug killed significant numbers of parasites.

Rather than developing new drugs, a second research team is testing an old drug used for gout against leishmaniasis. Under the World Health Organization auspices, Joseph Marr and Randolph Berens of the University of Colorado Health Sciences Center in Denver and their colleagues are administering the gout drug, allopurinol, in combination with antimony, a standard treatment for leishmaniasis, to more than 400 leishmaniasis patients in South America. Their findings, soon to appear in the AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, reveal the two drugs together work far better than either drug alone. The researchers are also conducting studies that phase out the antimony, which is highly toxic and needs to be given intravenously. Allopurinol is nontoxic to humans, and the Colorado team has developed an oral form of the drug. Says Marr, "It is kind of ideal."